The two major objectives of this project are to elucidate the function of the descending bulbospinal serotonergic system in controlling motor reflexes, and to further define the role of GABA in modulating primary afferent terminal polarization. The immediate aims for the coming year are to further define the pharmacology of the bulbospinal pathway (believed to be serotonergic) which induces a long-latency depolarization of primary afferent terminals, and to explore the basis for the differential pharmacological response between the spontaneous antidromic and segmentally evoked dorsal root reflexes. Pharmacological agents which alter the synthesis, storage, release or metabolism of serotonin or GABA will be investigated. Electrophysiological dissections will be carried out to localize the site of drug action. These will involve measurement of afferent terminal polarization using D.C. shifts, excitability testing and evoked potentials combined with localized drug application. In addition, the endogenous levels of 5-HT and/or GABA will be carefully monitored for changes induced by drug administration. In the process of carrying out this study, important evidence should be produced of or against the transmitter function of 5-HT and GABA in the systems controlling afferent terminal polarization.